Is propofol the perfect hypnotic agent for procedural sedation in neonates?

Introduction: Following the landmark observations on the relevance of adequate analgesia and sedation in neonates, neonatologists are in search for short acting agents for procedural sedation. Propofol (2,6 di-isopropylphenol) is considered to be a short acting anaesthetic that is both rapid in onset and short in duration after cessation, but data on pharmacokinetics and metabolism in neonates were absent. Methods: In 3 consecutive studies, data on propofol pharmacokinetics and metabolism were collected in neonates after single intravenous (3 mg/kg) bolus administration. Results: Median propofol clearance (19.6 mL kg^-1 min^-1) is significantly lower and interindividual variability (range 3.7-78 mL kg^-1 min^-1) in propofol clearance in neonates is extensive. Simultaneous introduction of postmenstrual and postnatal age as covariates resulted in a reduction of this interindividual clearance from 322 to 84 %. Finally, differences in clearance are due to limited capacity for glucuronidation in neonates, only in part compensated by hydroxylation. Conclusions: Clinicians should remain careful with propofol in neonates because of the reduced clearance and extensive interindividual variability. We strongly dissuade the use of continuous or repeated intermittent administration of propofol in the first weeks of life and suggest to study the pharmacodynamics of single bolus administration of propofol in neonates.